Successful allergen-specific immunotherapy (AIT) is associated with a marked decrease in symptoms on allergen exposure, a reduced requirement for 'rescue' anti-allergic drugs and improvement in patients' quality of life. These benefits persist for at least several years following discontinuation of immunotherapy - the hallmark of clinical and immunological tolerance. AIT has been shown to modulate both innate and adaptive immunological responses. Early suppression of innate effector cells of allergic inflammation (mast cells, basophils), regulation of pro-allergic T helper 2 type (Th 2) responses and IgE+ B cell responses have been shown to occur both in the tissue and in the peripheral blood during AIT. The allergen-tolerant state is associated with local and systemic induction of distinct populations of allergen-specific T regulatory cells including IL-10+ Tregs (Tr1 cells), TGF-β+ Tregs and FoxP3+ memory T regs. B cells are switched in favour of producing IgG (particularly IgG4) antibodies and associated blocking activity for IgE-dependent events, including basophil activation and IgE-facilitated allergen binding to B cells. An induction of IL-10+ B regulatory cells and alterations in dendritic cell subsets have also recently been described. These events are followed by the induction of T regulatory cells, suppression of allergen-specific T cell proliferation and immune deviation from Th2 in favour of Th1 responses. Alternative mechanisms of tolerance include apoptosis/deletion of antigen-specific memory Th2 cells and/or a failure of co-stimulation leading to T cell anergy.

IL-35 and iT35 cells are potential novel immune regulators induced by SLIT. The clinical relevance of SLIT can be underscored by restoration of protective iT35 cells.

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Tumor-specific peptide-pulsed dendritic cells (DC) were administered via different routes to a group of patients with head and neck cancers. The migration and homing patterns of such antigen-stimulated cells was carefully studied employing single photon emission computed tomography (SPECT). The DC administered directly into the nasal submucosa quickly migrated very rapidly to the regional neck lymph nodes in the neck. However, after inoculation of the cells into the palatine tonsils, the DCs remained close to the site of administration and did not migrate to the regional lymph nodes or to other mucosal regions. After nasal submucosal administration of the DC, tumor-antigen-specific cytotoxic T cells were detected in the ipsilaterals but not in the contra lateral lymph nodes. These results suggest that after antigen processing, the regional lymph nodes serve as inductive sites for development of mucosal immune responses and for induction of memory cells during the local immunological responses in the nasopharyngeal-associated lymphoid tissue in man.

Background: House dust mite (HDM) respiratory allergy is a common and burdensome

Initiating treatment with FP and adding FEX might lead to improved outcomes for nasal symptoms in comparison with the same drugs administered in the reverse order.

SUMMARYInterleukin (IL)-10 is known to be a multifunctional cytokine. This study was designed to evaluate the role of IL-10 during respiratory syncytial virus (RSV) infection using a C57BL/6 transgenic (TG) mouse model in which the expression of murine IL-10 cDNA was regulated by a human salivary amylase promoter (IL-10 TG mice). These mice expressed a large amount of IL-10 in the nasal mucosa and in salivary glands. Viral replication in the respiratory tract after intranasal infection with RSV was suppressed signi®cantly in IL-10 TG mice compared to non-transgenic controls. This suppression was IL-10 speci®c, because it was prevented by treating mice with neutralizing anti-IL-10 antibodies. We also found that IL-10-stimulated T cells displayed cytotoxic activity against infected murine nasal epithelial cells. Previous data indicated that IL-10 induces Fas ligand (L) expression on mouse T cells. Taken together, these data suggest that Fas/Fas L mediated cytotoxicity is involved in the suppression of RSV replication observed in IL-10 TG mice after intranasal infection.

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